Serum Concentrations of Angiopoietin-2 and Soluble fms-Like Tyrosine Kinase 1 (sFlt-1) Are Associated with Coagulopathy among Patients with Acute Pancreatitis

Paulina Dumnicka,Piotr Ceranowicz,Zygmunt Warzecha,Marek Kuźniewski,Krzysztof Gil,Ryszard Drożdż,Małgorzata Mazur-Laskowska,Joanna Bonior,Mateusz Sporek,Artur Dembiński,Beata Kuśnierz-Cabala

doi:10.3390/ijms18040753

Abstract

In severe acute pancreatitis (SAP), systemic inflammation leads to endothelial dysfunction and activation of coagulation. Thrombotic disorders in acute pancreatitis (AP) include disseminated intravascular coagulation (DIC). Recently, angiopoietin-2 and soluble fms-like tyrosine kinase 1 (sFlt-1) were proposed as markers of endothelial dysfunction in acute states. Our aim was to assess the frequency of coagulation abnormalities in the early phase of AP and evaluate the relationships between serum angiopoietin-2 and sFlt-1 and severity of coagulopathy. Sixty-nine adult patients with AP were recruited: five with SAP, 15 with moderately severe AP (MSAP) and 49 with mild AP. Six patients were diagnosed with DIC according to International Society on Thrombosis and Haemostasis (ISTH) score. All patients had at least one abnormal result of routine tests of hemostasis (low platelet count, prolonged clotting times, decreased fibrinogen, and increased D-dimer). The severity of coagulopathy correlated with AP severity according to 2012 Atlanta criteria, bedside index of severity in AP and duration of hospital stay. D-dimers correlated independently with C-reactive protein and studied markers of endothelial dysfunction. Angiopoietin-2, D-dimer, and ISTH score were best predictors of SAP, while sFlt-1 was good predictor of MSAP plus SAP. In clinical practice, routine tests of hemostasis may assist prognosis of AP.

Highlights

Acute pancreatitis (AP) is an inflammatory disorder, characterized by a spectrum of severity, ranging from mild disease in most patients, to severe life-threatening condition [1,2]
The diagnosis of disseminated intravascular coagulation (DIC) was significantly associated with more severe acute pancreatitis (AP), higher bedside index of severity in AP (BISAP) [25] and Glasgow [26] severity scores, longer hospital stays, and higher mortality (Table 1)
Patients subsequently diagnosed with DIC had longer prothrombin times and higher plasma concentrations of D-dimer at admission, as well as higher serum urea (Table 1)

Summary

Introduction

Acute pancreatitis (AP) is an inflammatory disorder, characterized by a spectrum of severity, ranging from mild disease in most patients, to severe life-threatening condition [1,2]. Severe course of AP is associated with excessive systemic inflammation, involving systemic activation and dysfunction of endothelial cells, leading to vascular leak syndrome and organ failure [4]. Flt-1 is a receptor for vascular endothelial growth factor and placental growth factor, its soluble form (sFlt-1) acts as a decoy receptor [14]. Both angiopoietin-2 and sFlt-1 may be considered markers of endothelial dysfunction in acute states. We have previously reported the associations between serum concentrations of angiopoietin-2 and the development of acute kidney injury and renal failure in the course of AP as well as the severity of AP [7]. We have reported the association between serum sFlt-1 concentrations in the early phase of AP and the severity of the disease [8]

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